miRNA-200c inhibits invasion and metastasis of human non-small cell lung cancer by directly targeting ubiquitin specific peptidase 25

Abstract

BackgroundGrowing evidence indicates that miR-200c is involved in carcinogenesis and tumor progression in non-small-cell lung cancer (NSCLC). However, its precise biological role remains largely elusive.MethodsThe functions of miR-200c and USP25 in migration/invasion and lung metastasis formation were determined by transwell and tail vein injection assays, respectively. The potential regulatory targets of miR-200c were determined by prediction tools, correlation with target protein expression, and luciferase reporter assay. The mRNA expression levels of miR-200c and USP25 were examined in NSCLC cell lines and patient specimens using quantitative reverse transcription-PCR. The protein expression levels of USP25 were examined in NSCLC cell lines and patient specimens using western blot and immunohistochemical staining.ResultsWe demonstrated that over-expression of miR-200c inhibited NSCLC cells migration, invasion, epithelial-mesenchymal transition (EMT) in vitro and lung metastasis formation in vivo. Further studies revealed that USP25 was a downstream target of miR-200c in NSCLC cells as miR-200c bound directly to the 3’-untranslated region of USP25, thus reducing both the messenger RNA and protein levels of USP25. Silencing of the USP25 gene recapitulated the effects of miR-200c over-expression. Clinical analysis indicated that miR-200c was negatively correlated with clinical stage, lymph node metastasis in NSCLC patients. Moreover, USP25 protein and mRNA level expressions were higher in NSCLC patients, compared to healthy control, and correlated with clinical stage and lymphatic node metastasis.ConclusionsThese findings indicate that miR-200c exerts tumor-suppressive effects for NSCLC through the suppression of USP25 expression and suggests a new therapeutic application of miR-200c in the treatment of NSCLC.

Demethylation drug 5-Aza-2′-deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro

“…Liu et al (13) identified that miR-200c inhibited invasion, migration and proliferation of bladder cancer cells. Li et al (25) showed that miR-200c inhibited metastasis and invasion of human non-small cell lung cancer cells (25). Therefore, the present study expanded the current understanding of miR-200c functioning in human cancer.…”

“…MicroRNAs (miRs) are a type of small non-coding RNA (19)(20)(21)(22)(23)(24)(25) nucleotides) that possess prominent roles in the regulation of genes (6). MiRs typically inhibit gene expression by directly binding the 3'-untranslated region of their target messenger (m)RNAs, causing repression of translation or mRNA degradation (7).…”

USP25 regulates Wnt signaling by controlling the stability of tankyrases

“…First, the levels of USP25 mRNAs are significantly increased in breast cancer tissues and non-small cell lung cancer (NSCLC) tissues as compared with adjacent tissues (Deng et al 2007;Li et al 2014), although the mechanisms that lead to this up-regulation remain to be elucidated. Second, USP25 can promote cell growth and tumor metastasis.…”

Expression of ubiquitin specific peptidase and ATG7 genes in U87 glioma cells upon glutamine deprivation

“…It is released from degraded proteins by disassembly of the polyubiquitin chains, which is mediated by ubiquitin-specific proteases, members of the ubiquitin-specific processing family of proteases for deubiquitination of proteins [7][8][9]. E3 ubiquitin ligases and deubiquitylases play an important role in cancer [7,10,11].…”